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1.
Dev Comp Immunol ; 157: 105179, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38614378

RESUMEN

Marine sponges, including the crumb of bread sponge, Hymeniacidon sinapium, display allorejection responses to contact with conspecifics in both experimental and natural settings. These responses have been used to infer immunocompetence in a variety of marine invertebrates. However, larvae and juveniles from several marine sponge species fuse and form chimeras. Some of these chimeras persist, whereas others eventually break down, revealing a period of allogeneic non-responsiveness that varies depending on the species. Alternatively, for H. sinapium, most pairs of sibling post-larvae and juveniles that settle in contact initiate immediate allorecognition and show the same morphological response progression as the adults. This indicates that allorecognition and response occurs during early metamorphosis. Results from H. sinapium and other sponge species, in addition to annotations of sponge genomes, suggest that allorecognition and immunocompetence in sponges are mediated by distinct systems and may become functional at different times during or after metamorphosis for different species. Consequently, allorecognition may not be a good proxy for the onset of immunocompetence.

2.
Cureus ; 16(2): e54241, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38496054

RESUMEN

Laryngeal mycosis, a condition often overlooked in systemically immunocompetent individuals, requires heightened clinical vigilance for accurate diagnosis. The disease mimics symptoms of other laryngeal conditions such as gastroesophageal reflux, granulomatous disease, keratosis, and glottic malignancies, with risk factors including prolonged use of antibiotics, inhaled steroids, and smoking. Clinically, it presents with variable symptoms including hoarseness, and occasionally pain, dysphagia, and odynophagia. Diagnosis involves the observation of hyperkeratosis, notably when intraepithelial neutrophils are present, prompting further investigation for fungal elements through specialized staining. Effective management encompasses prolonged systemic antifungal treatment and the elimination of predisposing factors to prevent recurrence or treatment failure. Despite its potential to mimic a range of laryngeal diseases, laryngeal mycosis remains a less considered differential diagnosis. This is compounded by the commonality of risk factors in the general population, including prolonged antibiotic use, inhaled steroid therapy, and smoking habits, which may predispose individuals to fungal infections of the larynx. Furthermore, the necessity for a high index of suspicion and specialized diagnostic techniques, such as the identification of hyperkeratosis with intraepithelial neutrophils through biopsy and specialized staining for fungal elements, underscores the complexity of diagnosing this condition. The rationale for documenting this case report is multifaceted, primarily focusing on the fact that laryngeal mycosis is rare among immunocompetent patients leading to under-recognition of laryngeal mycosis in systemically immunocompetent individuals and the diagnostic challenges it presents. Additionally, the documentation seeks to emphasize the critical need for comprehensive treatment approaches, including prolonged systemic antifungal therapy and the identification and elimination of predisposing factors, to ensure effective management and prevent recurrence.

3.
J Infect ; 88(3): 106133, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38432583

RESUMEN

OBJECTIVES: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.


Asunto(s)
Gripe Humana , Trasplante de Riñón , Tétanos , Humanos , Persona de Mediana Edad , Anciano , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Gripe Humana/tratamiento farmacológico , Formación de Anticuerpos , Vacunas contra la COVID-19 , Tétanos/prevención & control , Tétanos/tratamiento farmacológico
4.
Parasit Vectors ; 17(1): 164, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555448

RESUMEN

BACKGROUND: The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known. METHODS: In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual. RESULTS: We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus. CONCLUSIONS: Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.


Asunto(s)
Infestaciones por Pulgas , Enfermedades de los Roedores , Siphonaptera , Garrapatas , Animales , Femenino , Masculino , Sciuridae/parasitología , Infestaciones por Pulgas/veterinaria , Testosterona/fisiología , Inmunocompetencia/fisiología
5.
Viral Immunol ; 37(2): 89-100, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38301195

RESUMEN

Herpesvirus of turkey (HVT) increases activation of T cells in 1-day-old chickens when administered in ovo. This study evaluated whether adding cytosine-guanosine oligodeoxynucleotides (CpG ODNs) to the HVT vaccine could enhance the adjuvant effect of HVT. We used a CpG ODN dose of 10 µg per egg. The experimental groups were (1) diluent-only control (sham), (2) HVT, (3) HVT+CpG ODN, (4) HVT+non-CpG ODN, (5) CpG ODN, and (6) non-CpG ODN control. Cellular response evaluation included measuring the frequencies of macrophages (KUL01+MHC-II+), gamma delta T cells (γδTCR+MHC-II+), CD4+, and CD8+ T cell subsets, including double-positive (DP) cells. In addition, CD4+ and CD8+ T cell activation was evaluated by measuring the cellular expression of major histocompatibility complex class II (MHC-II), CD44 or CD28 costimulatory molecules. An adjuvant effect was considered when HVT+CpG ODN, but not HVT+non CpG ODN, or CpG ODN, or non-CpG ODN, induced significantly increased effects on any of the immune parameters examined when compared with HVT. The findings showed that (1) HVT vaccination induced significantly higher frequencies of γδ+MHC-II+ and CD4+CD28+ T cells when compared with sham chickens. Frequencies of DP and CD4+CD28+ T cells in HVT-administered birds were significantly higher than those observed in the non-CpG ODN group. (2) Groups receiving HVT+CpG ODN or CpG ODN alone were found to have significantly increased frequencies of activated CD4+ and CD8+ T cells, when compared with HVT. Our results show that CpG ODN administration in ovo with or without HVT significantly increased frequencies of activated CD4+ and CD8+ T cells.


Asunto(s)
Herpesviridae , Vacunas , Animales , Pollos , Linfocitos T CD8-positivos , Antígenos CD28 , Adyuvantes Inmunológicos , Oligodesoxirribonucleótidos , Carne
6.
Nutrients ; 16(3)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38337682

RESUMEN

The pro-hormone vitamin D3 is an important modulator of both innate and adaptive immunity since its biologically active metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates via the transcription factor VDR (vitamin D receptor) the epigenome and transcriptome of human immune cells and controls in this way the expression of hundreds of vitamin D target genes. Since the myeloid linage of hematopoiesis is epigenetically programmed by VDR in concert with the pioneer factors PU.1 (purine-rich box 1) and CEBPα (CCAAT/enhancer binding protein α), monocytes, macrophages, and dendritic cells are the most vitamin D-sensitive immune cell types. The central role of the immune system in various aging-related diseases suggests that immunocompetence describes not only the ability of an individual to resist pathogens and parasites but also to contest non-communicative diseases and the process of aging itself. In this review, we argue that the individual-specific responsiveness to vitamin D relates to a person's immunocompetence via the epigenetic programming function of VDR and its ligand 1,25(OH)2D3 during hematopoiesis as well as in the periphery. This may provide a mechanism explaining how vitamin D protects against major common diseases and, in parallel, promotes healthy aging.


Asunto(s)
Receptores de Calcitriol , Vitamina D , Humanos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Regulación de la Expresión Génica , Colecalciferol , Vitaminas , Factores de Transcripción/metabolismo
7.
An. sist. sanit. Navar ; 47(1): e1067, 07-02-2024. ilus
Artículo en Español | IBECS | ID: ibc-231768

RESUMEN

La meningitis criptocócica es una infección infrecuente y con alta morbimortalidad, cuya presentación en pacientes inmunocompetentes es excepcional. Presentamos el caso de un varón de 67 años que ingresó por un cuadro subagudo de alteración de la marcha e incontinencia urinaria. El examen neurológico reveló incapacidad para mantenerse en pie y deterioro de la memoria. Las pruebas de imagen craneales mostraron hidrocefalia tetraventricular obstructiva con áreas de gliosis en los pedúnculos cerebelosos. Se realizó tratamiento endoscópico de la hidrocefalia, con toma de muestras de líquido cefalorraquídeo en las que se observó crecimiento de Cryptococcus neoformans. El paciente mejoró con el tratamiento endoscópico y tras completar la terapia antifúngica intravenosa con anfotericina B liposomal y fluconazol durante diez semanas. La meningitis criptocócica en pacientes inmunocompetentes se trata con antifúngicos. En raras ocasiones se presenta con hidrocefalia, situación que requiere tratamiento quirúrgico mediante derivaciones del líquido cefalorraquídeo o técnicas endoscópicas. (AU)


Cryptococcal meningitis is an infrequent infection with high morbidity and mortality. Its presentation in immuno-competent patients is rare.We present the case of a 67-year-old male who was admitted for subacute symptoms of gait disturbance and urinary incontinence. Neurological examination revealed inability to stand and memory impairment. Cranial im-aging showed obstructive tetraventricular hydrocephalus with areas of gliosis in the cerebellar peduncles. Endo-scopic treatment of hydrocephalus was performed and cerebrospinal fluid samples taken revealing the growth of Cryptococcus neoformans. The patient improved with the endoscopic treatment and after completing intravenous antifungal therapy with liposomal amphotericin B and flu-conazole for ten weeks.Antifungals are used to treat cryptococcal meningitis in immunocompetent patients. On rare occasions, it presents with hydrocephalus, a situation that requires surgical treat-ment using cerebrospinal fluid diversions or endoscopic techniques. (AU)


Asunto(s)
Humanos , Masculino , Anciano , Meningitis Criptocócica/diagnóstico por imagen , Meningitis Criptocócica/tratamiento farmacológico , Huésped Inmunocomprometido , Ventriculostomía , Cryptococcus , Hidrocefalia , Antifúngicos/uso terapéutico
8.
J Exp Zool A Ecol Integr Physiol ; 341(3): 264-271, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38213098

RESUMEN

Immune responses can increase survival, but they can also incur a variety of costs that may lead to phenotypic trade-offs. The nature of trade-offs between immune activity and other components of the phenotype can vary and depend on the type and magnitude of immune challenge, as well as the energetic costs of simultaneously expressing other traits. There may also be sex-specific differences in both immune activity and trade-offs, particularly with regard to energy expenditure that might differ between males and females during the breeding season. Females are generally expected to invest less in nonspecific immune responses compared to males due to differences in the allocation of resources to reproduction, which may lead to sex differences in the metabolic costs of immunity. We tested for sex-specific differences in metabolic costs of different types of immune challenges in Anolis carolinensis lizards, including lipopolysaccharide (LPS) injection and wounding. We also tested for differences in immune prioritization by measuring bacterial killing ability (BKA). We predicted males would show a greater increase in metabolism after immune challenges, with combined immune challenges eliciting the greatest response. Furthermore, we predicted that metabolic costs would result in decreased BKA. LPS injection increased the resting metabolic rate (RMR) of males but not females. Wounding did not affect RMR of either sex. However, there was an inverse relationship between BKA and wound healing in LPS-injected lizards, suggesting dynamic tradeoffs among metabolism and components of the immune system.


Asunto(s)
Lagartos , Femenino , Animales , Masculino , Lagartos/fisiología , Lipopolisacáridos/farmacología , Metabolismo Energético/fisiología , Metabolismo Basal , Sistema Inmunológico
9.
Mult Scler ; : 13524585231221680, 2024 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-38247156

RESUMEN

BACKGROUND: Fungal infections of the central nervous system usually affect immunocompromised patients. Primary Aspergillus myelitis has never been described. REPORT: A 45-year-old immunocompetent male with subacute paraplegia was treated for inflammatory myelitis before clinical deterioration requiring mechanical ventilation. Purulent meningitis preceded the formation of a paraspinal nodule biopsied by neurosurgery. Histopathological analysis revealed the presence of fungal hyphae, and polymerase chain reaction was positive for Aspergillus fumigatus. No cause of immunodeficiency was identified in this patient. DISCUSSION: Primary Aspergillus myelitis may be confused with inflammatory myelitis and should be considered even in the absence of apparent immunosuppression.

10.
Ecol Evol ; 14(1): e10764, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38187919

RESUMEN

Sexes of a species may show different characteristics beyond the differences in their sexual organs and such sexual dimorphism often occurs in the level of immune response when exposed to pathogens (immunocompetence). In general, females have increased longevity relative to males, which is associated with higher immunocompetence. However, males have higher immunocompetence in some species, such as pipefishes and seahorses. Experimental evidence suggests that this could be because males, rather than females, carry fertilized eggs to birth in these species. This observation suggests that an increase in immunocompetence may be related to the level of parental investment and not to a particular sex. We use state-dependent life-history theory to study optimal investment in offspring production relative to parent immunocompetence, varying the relative time that a parent spends in brooding or pregnancy within a breeding cycle. When offspring is dependent on a parent's survival for a large part of the breeding cycle, we predict higher investments in immunity and longer life expectancies.

11.
Poult Sci ; 103(3): 103383, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38176370

RESUMEN

The study examined the effects of feeding broiler breeder pullets hydrolyzed whole yeast (HY) from hatch to 22 wk of age (WOA). A total of 524-day-old Ross 708 pullets were placed in floor pens (∼24 birds/pen) for the starter (0-4 WOA) and grower (5-18 WOA) phases, then transferred to the egg production facility and redistributed to ∼20 birds/pen for the prelay phase (19-22 WOA). Two diets were allocated to pens (0-18 WOA; n = 11) and (19-22 WOA; n-12). The diets were a control corn and soybean meal diet formulated to meet specifications and control plus 0.05% HY (HY). Birds had ad libitum access to feed in the first week and daily feed allocation based on pen BW from 2 WOA. Birds had free access to water throughout the trial. Body weight (BW) and uniformity (BW CV) were monitored. Boosters for infectious bronchitis and New Castle disease vaccines were administered at 18 WOA, and samples of pullets bled for antibody titer 5-day later. One pullet/pen was randomly selected, weighed, bled for plasma biochemistry, and necropsied for organ weights, ceca digesta for short-chain fatty acids (SCFA), and leg bones morphometry. In the starter and grower phases, birds fed HY were lighter and gained less (P < 0.05) than control birds. However, there were no diet effects (P > 0.05) on growth, the BW prelay phase, or BW uniformity throughout the trial. There were no (P > 0.05) diet effects on breast, gastrointestinal, liver and bursa weights, serum antibody titers, plasma biochemistry, SCFA and bone attributes. However, pullets fed HY had heavier (P = 0.047) spleen and tended to have lower (P = 0.080) plasma concentrations of aspartate aminotransferase (AST) relative to control pullets. In conclusion, the parameters assessed showed no negative consequences of feeding HY to broiler breeder pullets. However, effects on the spleen and plasma AST may indicate modest modulation of immunity and metabolism. The impact of the provision of HY during broiler breeder pullet phase on reproductive performance and chick quality should be investigated.


Asunto(s)
Saccharomyces cerevisiae , Levadura Seca , Animales , Femenino , Pollos , Hígado , Troglitazona
12.
Res Vet Sci ; 166: 105095, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38016220

RESUMEN

Secondary sex traits (SSTs) can favour males in intra-sexual competition, allowing females to reliably assess their quality. They can also be connected to other aspects of fitness, such as resistance to parasites and pathogens, as parasites have negative effects on the development of SSTs. Antlers are one of the most recognizable examples of SSTs whose development is regulated by testosterone and reflects the actual condition of the bearer. Elevated testosterone can exaggerate the size of SSTs while impairing the function of the immune system ("The Immunocompetence Handicap Hypothesis") posing a trade-off between antler development and immune function. In this study, we experimentally manipulated the parasite load in captive red deer (Cervus elaphus) males with Ivermectin during antler development for two consecutive years. Expecting an inverse proportionality between parasite load and antler size, we hypothesized the treated deer to have larger antlers than the untreated ones. Our results showed that, following the immunocompetence handicap hypothesis, parasite load was positively associated with testosterone levels. However, the application of Ivermectin suppressed the parasite load of the treated animals but did not lead to the development of larger antlers. Instead, it significantly suppressed the concentration of testosterone in the treated animals, whilst the animals that had higher testosterone also had the highest parasite load. Our findings show that Ivermectin can potentially decrease the levels of testosterone and, consequently, antler size. These findings have important implications for the management of captive populations, especially in contexts where the development of large trophies is desired.


Asunto(s)
Cuernos de Venado , Ciervos , Femenino , Masculino , Animales , Testosterona/farmacología , Ivermectina/farmacología , Carga de Parásitos/veterinaria
13.
Pediatr Dermatol ; 41(1): 148-149, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37518420

RESUMEN

A healthy 6-month-old girl presented with plantar keratoderma-like lesions unresponsive to topical corticosteroids. Nocturnal pruritus in 13 relatives, presence of burrows on clinical exam, and the positive scabies preparation led to the diagnosis of crusted scabies. She was successfully treated with topical and oral scabicides. Crusted scabies is a severe form of Sarcoptes scabiei infection uncommon in immunocompetent subjects, in whom previous corticosteroid use may favor its occurrence.


Asunto(s)
Escabiosis , Animales , Lactante , Femenino , Humanos , Escabiosis/diagnóstico , Escabiosis/tratamiento farmacológico , Sarcoptes scabiei , Glucocorticoides/uso terapéutico , Prurito , Esteroides/uso terapéutico
14.
J Proteomics ; 291: 105045, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-37939914

RESUMEN

BACKGROUND: Lymph node metastasis (LNM) from Breast cancer (BC) is commonly seen in BC progression. Currently, the identification of genes linked with LNM in BC remains in mystery. METHODS: Genes related to BC LNM were screened, and a risk model was constructed based on LASSO-Cox analysis. Combined with the Kaplan-Meier curve, the ability of riskscore to distinguish different baseline characteristics was evaluated, and model was verified by the receiver operating characteristic (ROC) curve. The expression levels of prognostic marker genes were analyzed by qRT-PCR and western blot (WB). RESULTS: A higher survival rate and longer survival time in low-risk BC patients. The 1, 3 and 5 year AUC values of the training set were 0.79, 0.74, and 0.73, respectively. Results for the validation set was similar to the training set. The differentially expressed genes between the high- and low-risk groups were significantly enriched in immune pathways. In addition, the low-risk group had higher levels of immune infiltration. qRT-PCR and WB results showed that in BC, CDH10, SMR3A, POU3F2, and FABP7 were down-regulated, and LHX1 was up-regulated. CONCLUSIONS: We built a prognostic model of BC based on LNM-related genes, proffering evaluation for prognosis and precise cure of BC. SIGNIFICANCE: At present, the genes related to lymph node metastasis in BC are still largely unknown and need to be further explored. Searching for potential lymph node metastasis-related genes of BC will provide meaningful biomarkers for BC treatment. Based on TCGA-BRCA data, we established an effective 11-gene prognostic risk model that could predict patient outcomes independently. Our model could classify BC patients and distinguish patients with poor prognosis effectively. Besides, the feature genes we identified might exert a predictive function in immunotherapy. The results of this study provide a new reference for the prognosis and treatment of BC patients with lymph node metastasis.


Asunto(s)
Neoplasias de la Mama , Linfoma , Humanos , Femenino , Neoplasias de la Mama/genética , Metástasis Linfática , Pronóstico , Mama
15.
Vaccines (Basel) ; 11(12)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38140158

RESUMEN

To investigate early immune responses and explore the optimal vaccination periods, Nile tilapia at 1, 7, 14, 21, 28, 35, and 42 days after yolk sac collapse (DAYC) were immersed in formalin-killed Streptococcus agalactiae vaccine (FKV-SA). A specific IgM was first detected via ELISA in the 21 DAYC larvae (0.108 g) at 336 h after vaccination (hav), whereas in the 28-42 DAYC larvae (0.330-0.580 g), the specific IgM could be initially detected at 24 hav. qRT-PCR analysis of the TCRß, CD4, MHCIIα, IgHM, IgHT, and IgHD genes in 21-42 DAYC larvae immunized with the FKV-SA immersion route for 24, 168, and 336 hav revealed that the levels of most immune-related genes were significantly higher in the vaccinated larvae at all DAYCs than in the control larvae (p < 0.05) at 336 hav. Immunohistochemistry demonstrated stronger IgM signals in the gills, head kidney, and intestine tissues at 21, 28, and 35 DAYC in all vaccinated larvae compared with the control. Interestingly, at all DAYCs, FKV-SA larvae exhibited significantly higher survival rates and an increased relative percent survival (RPS) than the control after challenge with viable S. agalactiae, particularly in larvae that were immunized with FKV-SA at 168 and 336 hav (p < 0.05).

16.
J Immunother Cancer ; 11(11)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37963635

RESUMEN

BACKGROUND: The cancer stem cell theory proposes that tumor formation in vivo is driven only by specific tumor-initiating cells having stemness; however, clinical trials conducted to test drugs that target the tumor stemness provided unsatisfactory results thus far. Recent studies showed clear involvement of immunity in tumors; however, the requirements of tumor-initiation followed by stable growth in immunocompetent individuals remain largely unknown. METHODS: To clarify this, we used two similarly induced glioblastoma lines, 8B and 9G. They were both established by overexpression of an oncogenic H-RasL61 in p53-deficient neural stem cells. In immunocompromised animals in an orthotopic transplantation model using 1000 cells, both show tumor-forming potential. On the other hand, although in immunocompetent animals, 8B shows similar tumor-forming potential but that of 9G's are very poor. This suggests that 8B cells are tumor-initiating cells in immunocompetent animals. Therefore, we hypothesized that the differences in the interaction properties of 8B and 9G with immune cells could be used to identify the factors responsible for its tumor forming potential in immunocompetent animals and performed analysis. RESULTS: Different from 9G, 8B cells induced senescence-like state of macrophages around tumors. We investigated the senescence-inducing factor of macrophages by 8B cells and found that it was interleukin 6. Such senescence-like macrophages produced Arginase-1, an immunosuppressive molecule known to contribute to T-cell hyporesponsiveness. The senescence-like macrophages highly expressed CD38, a nicotinamide adenine dinucleotide (NAD) glycohydrolase associated with NAD shortage in senescent cells. The addition of nicotinamide mononucleotide (NMN), an NAD precursor, in vitro inhibited to the induction of macrophage senescence-like phenotype and inhibited Arginase-1 expression resulting in retaining T-cell function. Moreover, exogenous in vivo administration of NMN after tumor inoculation inhibited tumor-initiation followed by stable growth in the immunocompetent mouse tumor model. CONCLUSIONS: We identified one of the requirements for tumor-initiating cells in immunocompetent animals. In addition, we have shown that tumor growth can be inhibited by externally administered NMN against macrophage senescence-like state that occurs in the very early stages of tumor-initiating cell development. This therapy targeting the immunosuppressive environment formed by macrophage senescence-like state is expected to be a novel promising cancer therapeutic strategy.


Asunto(s)
Arginasa , NAD , Ratones , Animales , Arginasa/metabolismo , NAD/genética , NAD/metabolismo , Senescencia Celular , Macrófagos/metabolismo , Fenotipo , Modelos Animales de Enfermedad
17.
Environ Pollut ; 338: 122662, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37778488

RESUMEN

Concerns have grown worldwide about the potentially far-reaching effects of herbicides on functional biodiversity in agroecosystems. Repeated applications over time can lead to accumulation of residues in soil, water, and food and may have negative impacts on non-target organisms. However, the effects of herbicide residues on interspecific relationships, such as host-pathogen interactions, are poorly studied. In this study, we evaluated the effects of two different concentrations of a commercial pendimethalin-based formulation (PND), the residual contamination (S, 13 ppm) in treated soils and the maximum residue level allowed by the European Commission in cereals (EU, 0.05 ppm). We tested the effect of PND on the biological interaction between the mealworm beetle Tenebrio molitor Linnaeus, 1758 and the entomopathogenic fungus Beauveria bassiana Vuillemin, 1912 (Bb, strain KVL 03-144) at two concentrations (LC50 5 × 105 conidia mL-1 and LC100 1 × 107 conidia mL-1). We checked the survival of beetles exposed to PND or/and inoculated with B. bassiana, the expression of four antimicrobial peptides (AMPs), and finally how PND affects in vitro germination of fungus. The exposure to PND had no significant effects on the survival of either control or Bb-exposed beetles. In the mealworm beetle, upregulation of gene expression of the inducible AMPs Tenecin 1, 2, and 4 was observed in PND-treated beetles after inoculation with Bb, while the levels of the non-inducible AMP Tenecin 3 were similar between treatments. In conclusion, our findings demonstrate that admitted residual doses of currently used herbicides modify an important component of the inducible immune response of an insect. This did not translate into an effect on the survival to B. bassiana in our system. However, residual doses of the herbicide at 13 ppm may temporarily affect fungal germination. These results raise questions about the compatibility of bioinsecticides with synthetic pesticides and the effects of herbicide residues on host-pathogen interactions.


Asunto(s)
Beauveria , Escarabajos , Herbicidas , Tenebrio , Animales , Escarabajos/microbiología , Tenebrio/microbiología , Beauveria/fisiología , Herbicidas/farmacología , Expresión Génica , Control Biológico de Vectores
18.
R Soc Open Sci ; 10(8): 230579, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37564068

RESUMEN

Immunocompetence and reproduction are among the most important determinants of fitness. However, energetic and metabolic constraints create conflict between these two life-history traits. While many studies have explored the relationship between immune activity and reproductive fitness in birds and mammals inoculated with bacterial endotoxin, very few have focused on fish. Fish have been neglected in this area due, in part, to the claim that they are largely resistant to the immune effects of endotoxins. However, the present study suggests that they are susceptible to significant effects with respect to reproductive behaviour. Here, we examined the reproductive behaviour of male guppies following exposure to bacterial lipopolysaccharides (LPS) in comparison to that of male guppies in a control treatment. Additionally, we investigated the responses of females to these males. We show that although immune challenge does not suppress general activity in male guppies, it significantly reduces mating effort. While females showed no difference in general activity as a function of male treatments, they did exhibit reduced group cohesion in the presence of LPS-exposed males. We discuss this in the context of sickness behaviours, social avoidance of immune-challenged individuals and the effects of mounting an immune response on reproductive behaviour.

19.
J Therm Biol ; 116: 103640, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37542840

RESUMEN

Short Periods of Incubation During Egg Storage (SPIDES) approach improves chick quality and hatching rates. Also, embryonic thermal conditioning (TC) is a strategy for enhancing thermotolerance in avian species. Until now, evaluating the effect of either SPIDES or embryonic TC effects has only been separately conducted, so we hypothesized that combining TC and SPIDES may enhance the response of broilers to thermal stress. Eight hundred Ross broiler eggs were divided into two groups; the first one was kept under appropriate storage room conditions, S0 (control) The 2nd was subjected to SPIDES for 5 h at 37.8 ○C ± 0.1 three times at days 5, 10, and 15 (S1) after egg collection respectively. On the 14th day of incubation (DOI) each of the two main groups was randomly divided into two equal subgroups; the control one was left under the appropriate incubation settings (TC0) whereas the other received prenatal heat conditioning (TC1) at 39.5 ○C ± 0.1 for 6 h/d from the 14th to the 18th embryonic day (E), resulting finally in four experimental subgroups (S0TC0, S1TC0, S0TC1 & S1TC1). RESULTS: showed that SPIDES treatment improved the hatchability of the stored eggs by almost 20% compared to untreated eggs. A combination of SPIDES and TC (S1TC1) increased significantly the levels of Immunoglobulin (IgG and IgM) production at hatch and heat-stressed birds. Our findings revealed that the hepatic heat shock proteins (hsp70, 90 A,90 B, 60 and hspA9), antioxidants-related genes (CAT, and SOD2), and NADPH4 were significantly downregulated in the thermally conditioned group that challenged with thermal stress conditions. As opposed to that, the SPIDES group showed a significant increase in hepatic heat shock proteins, antioxidants-related genes, and NADPH4 when subjected to thermal-stress conditions. In conclusion, the combination of SPIDES and TC has a positive effect on some pre and post-hatch traits of broiler chicks. Under heat stress challenge, thermal conditioning can modify the expression of antioxidant-related genes and Hsps, leading to the enhanced acquisition of thermotolerance as evidenced by lower expression of Hsps and NADPH4. While SPIDES does not have a significant role in thermotolerance acquisition.


Asunto(s)
Pollos , Proteínas de Choque Térmico , Animales , Pollos/fisiología , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Antioxidantes/metabolismo , Respuesta al Choque Térmico , Inmunocompetencia
20.
Comp Immunol Microbiol Infect Dis ; 100: 102036, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37541170

RESUMEN

Feral birds residing close to urban settings exhibit higher immunocompetence against environmental pathogens than their counterparts in rural areas. In this study, we comprehensively evaluated the immunocompetence of five specific feral bird species and investigated the potential for interspecies transmission and pathogenicity of Avian orthoavulavirus-1 (AOAV-1) originating from the Anseriformes order. The immunocompetence assessment involved administering the phytohemagglutinin (PHA) test to individual groups of birds from rural and urban settings, measuring patagium thickness at specific time intervals (12, 24, 36, 48, and 60 h) following the administration of 0.1 mL (1 mg/mL) of PHA. Urban birds displayed significantly enhanced mean swelling responses, particularly urban pigeons, which exhibited a significant difference in patagium thickness at all-time intervals except for 24 h (p = 0.000, p = 0.12). Similarly, rural and urban quails and crows showed substantial differences in patagium thickness at all-time intervals except for 12 h (p = 0.542, p = 0.29). For the assessment of interspecies transmission potential and pathogenicity, each feral bird group was separately housed with naive broiler birds (n = 10 each) and challenged with a velogenic strain of AOAV-1 isolate (Mallard-II/UVAS/Pak/2016) at a dose of 1 mL (108 EID50/mL). Urban birds demonstrated higher resistance to the virus compared to their rural counterparts. These findings highlight the specific immunocompetence of feral bird species and their potential contributions to AOAV-1 transmission and pathogenicity. Continuous monitoring, surveillance, and strict implementation of biosafety and biosecurity measures are crucial for effectively controlling AOAV-1 spillover to the environment and wild bird populations in resource-limited settings, particularly Pakistan.


Asunto(s)
Animales Salvajes , Pollos , Animales , Virus de la Enfermedad de Newcastle/fisiología , Patos , Inmunocompetencia
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